Leptin, secreted by adipocytes in proportion to body fat mass
The saturated fatty acid palmitate (16:0) induces
NF-κB signaling through a TLR4-dependent mechanism
18:0 (stearic) and longer
saturated fatty acids as well as linolenic acid (18:3) increased proinflammatory cytokines, ER stress markers, and TLR4 activation
(SOCS)-3. A member of a protein family originally characterized as negative feedback regulators
of inflammation (13, 37), SOCS3 inhibits insulin and leptin signaling
IKKβ signaling in discrete neuronal subsets appears
to be required for both hypothalamic inflammation and excess weight gain to occur during HF feeding
the paradoxical observation that hyperphagia and weight gain occur when hypothalamic inflammation is induced
by HF feeding, yet when it occurs in response to systemic or local inflammatory processes (e.g. administration of endotoxin), anorexia and weight loss are the rule
, serves as a circulating signal of energy stores in part
by providing feedback inhibition of hypothalamic orexigenic pathways [e.g. neurons that express neuropeptide Y and agouti-related peptide (AgRP)]
and stimulating anorexigenic neurons
signals from Toll-like receptors (TLRs), evolutionarily conserved pattern recognition molecules critical for
detecting pathogens, amplified through signaling intermediates such as MyD88 activate the inhibitor of κB-kinase-β (IKKβ)/nuclear
factor-κB (NF-κB), c-Jun N-terminal kinase (Jnk) and other intracellular inflammatory signals in response to stimulation by
circulating saturated fatty acids